Systems and Methods for Activating and Controlling Impedance-Based Detection Systems of Implantable Medical Devices

ABSTRACT

Techniques are provided for use with implantable medical devices for addressing encapsulation effects, particularly in the detection of cardiac decompensation events such as heart failure (HF) or cardiogenic pulmonary edema (PE.) In one example, during an acute interval following device implant, cardiac decompensation is detected using heart rate variability (HRV), ventricular evoked response (ER) or various other non-impedance-based parameters that are insensitive to component encapsulation effects. During the subsequent chronic interval, decompensation is detected using intracardiac or transthoracic impedance signals. In another example, the degree of maturation of encapsulation of implanted components is assessed using impedance frequency-response measurements or based on the frequency bandwidth of heart sounds or other physiological signals. In this manner, impedance-based HF/PE detection systems can be activated as soon as component encapsulation has matured, without necessarily waiting until completion of a preset post-implant maturation interval, often set to forty-five days or more.

FIELD OF THE INVENTION

The invention generally relates to implantable medical devices, such aspacemakers, implantable cardioverter/defibrillators (ICDs) or cardiacresynchronization therapy devices (CRTs) and, in particular, totechniques for detecting and tracking heart failure (HF), cardiogenicpulmonary edema (PE) or related cardiac decompensation events withinpatients in which such devices are implanted.

BACKGROUND OF THE INVENTION

Cardiac decompensation generally refers to the failure of the heart tomaintain adequate blood circulation due, for example, to HF or othermedical ailments. A particularly severe form of heart failure iscongestive heart failure (CHF) wherein the weak pumping of the heartleads to build-up of fluids in the lungs and other organs and tissues.The build-up of fluids in the lungs due to poor heart function isreferred to as cardiogenic PE. Herein, HF, CHF and cardiogenic PE areall considered to be cardiac decompensation events.

It is highly desirable to detect cardiac decompensation events within apatient and to track the progression thereof using implantable medicaldevices so that appropriate therapy can be provided. At least sometechniques have been developed for detecting HF/PE events and deliveringresponsive therapy that exploit electrical impedance signals (or relatedsignals such as admittance or immittance) measured within the patient.

See, e.g., U.S. Patent Application 2010/0069778 of Bornzin et al.,entitled “System and Method for Monitoring Thoracic Fluid Levels basedon Impedance using an Implantable Medical Device”; U.S. Pat. No.7,628,757 to Koh, entitled “System and Method for Impedance-BasedDetection of Pulmonary Edema and Reduced Respiration using anImplantable Medical System”; and U.S. Pat. No. 7,272,443 to Min et al.,entitled “System and Method for Predicting a Heart Condition based onImpedance Values using an Implantable Medical Device.” See, also, U.S.patent application Ser. No. 11/558,194, of Panescu et al. filed Nov. 9,2006, entitled “Closed-Loop Adaptive Adjustment of Pacing Therapy basedon Cardiogenic Impedance Signals Detected by an Implantable MedicalDevice.” Still further, see U.S. Patent Application 2009/0287267 ofWenzel et al., entitled “System and Method for Estimating ElectricalConduction Delays from Immittance Values Measured using an ImplantableMedical Device,” which described techniques for using impedance toevaluate conduction delays that can be converted to LAP values fortracking HF.

Although impedance-based HF/PE techniques are generally effective duringa chronic implant phase beginning a few months after device implant,problems can arise during an acute phase during the first month or twofollowing device implant. During the acute phase, the electrodes used bythe device to detect impedance are subject to on-going tissueencapsulation. During that interval, changes in tissues surrounding theelectrodes—including tissues surrounding the housing of the deviceitself—can greatly affect the impedance values measured using theelectrodes, typically rendering impedance-based HF/PE detection systemsunreliable and unusable.

In this regard, the human body typically encapsulates the leads anddevice during the first thirty to sixty days following the implantation.The encapsulation tissue changes the local impedance characteristicssurrounding the lead electrodes, as well as the device housingelectrode. It is now believed that the majority of the impedancecharacteristics occur within about one centimeter of the electrodes usedto measure the impedance. Given that the majority of the signal occursnear the electrode and the encapsulation occurs on or near the surfaceof the electrode, it is expected that measured impedance signals willvary with changes in encapsulation. This applies to both transthoracicor intrathoracic impedance signals (measured between the device housingand electrodes on or within the heart) and intracardiac impedancesignals (measured between a pair of electrodes on or within the heart.)Herein, transthoracic impedance signals are also referred to as “PEimpedance signals,” since the transthoracic signals are used to detectPE. Intracardiac impedance signals are also referred to herein ascardiogenic impedance (CI) signals, since the intracardiac signalsexhibit variations representative of the beating of the chambers of theheart.

Moreover, the magnitude and duration of changes to impedance duringencapsulation can depend greatly on the individual patient's genetics,immune system, the health of the patient, the affects of the steroids,patient medications, and many other factors. Given all of theseparameters, it is currently not feasible to determine a priori whenimpedance signals will stabilize. Therefore, at least somestate-of-the-art HF/PE impedance detection systems are programmed toignore the first forty-five days or so of impedance data, post-implant.That is, a moratorium is imposed within algorithms of the device againstcollecting impedance data during that initial interval for the purposesof detecting HF/PE. (Impedance may be measured for other reasons, suchas to detect lead failure.) Furthermore, many HF/PE impedance detectionsystems employ a fourteen day moving average as a baseline for use indetecting HF/PE. Therefore, once the encapsulation process is complete,such systems need an additional fourteen days to fully stabilize beforeHF/PE detection can begin, which means that such systems do not detector respond to cardiac decompensation events during the first sixty daysafter implant, leaving the patient potentially vulnerable. It is notedthat not all devices ignore the first forty-five days of impedance data.Some devices may ignore only the first thirty days of data. Nor do alldevices employ a fourteen day “moving average” window. Typically,though, HF/PE impedance-based detection systems are not activated untilabout forty-five to sixty days post implant.

It would be desirable to provide techniques for detecting HF, PE orother cardiac decompensation events that can be employed during thepost-implant acute phase. It would also be desirable to determine withina particular patient whether impedance-based HF/PE detection systems canbe safely activated before completion of the typical forty-five tosixty-day post-implant interval. It is to these ends that aspects of thepresent invention are directed.

SUMMARY OF THE INVENTION

In accordance with a first aspect of the invention, an exemplary methodis provided for use with an implantable medical device for addressingencapsulation effects, particularly in the detection of cardiacdecompensation events such as HF and cardiogenic pulmonary edema PE.Briefly, during an acute interval or phase following device implant,cardiac decompensation events are detected within the patient usingdetection parameters that are relatively insensitive to componentencapsulation effects, particularly various non-impedance baseddetection parameters. Then, following the acute interval, cardiacdecompensation events are detected using parameters that are relativelymore sensitive to component encapsulation effects, such as intracardiacimpedance (sometimes also referred to as “cardiogenic impedance” (CI))parameters or transthoracic (PE) impedance parameters. That is,following the acute interval, an otherwise conventional impedance-basedHF/PE detection system may be activated to take over HF/PE detection.

In an illustrative embodiment, the implantable device is a pacemaker,ICD or CRT device. The cardiac decompensation events that are detectedby the device include HF, CHF or cardiogenic PE. During the acuteinterval following device implant, cardiac decompensation is detectedbased on changes in heart rate variability (HRV), ventricular evokedresponse (ER), atrioventricular (AV/PV) delay and interventricular (VV)delay or other non-impedance based detection factors or parameters. Thedetection of a possible cardiac decompensation event during the acuteinterval can be supplemented or corroborated using patient posturesignals, patient activity signals or blood pressure signals. During thesubsequent chronic interval, cardiac decompensation is detected usingthe aforementioned CI or PE impedance parameters or based on somecombination of impedance and non-impedance based parameters.

In one particular example, the acute interval is deemed to have endedsixty days after implant—a time period set based on a forty-five daymaturation “moratorium” period combined with a subsequent fourteen-daymoving average window for collecting impedance measurements. In otherexamples, a shorter time period is set based on a thirty day moratoriumplus the fourteen-day moving average window. In still other examples,the end of the acute interval is detected based on impedance signalstability or other factors. In either case, the transition fromnon-impedance-based parameters (such as HRV and ER) to impedance-basedparameters (such as CI or PE signals) can be made gradually byincrementing the weight of impedance-based parameters relative to theweight of non-impedance-based parameters or can be performed immediatelyby simply switching from one to the other. Preferably, to detect acardiac decompensation event such as HF or cardiogenic PE, the deviceuses one or more thresholds against which the various measuredparameters are compared. These thresholds can vary based on the medicalconditions to be detected, the particular detection parameters used andon the amount of time since implant. Moving average impedance windowscan be exploited that gradually increase in duration up to a preferredlength upon the completion of the acute interval.

Thus, in accordance with the first aspect of the invention, varioustechniques are provided that allow for cardiac decompensation events tobe detected during the acute phase using, e.g., non-impedance-basedparameters such as HRV and ER.

In accordance with a second aspect of the invention, an exemplary methodis provided for use with an implantable medical device for determiningwhether the degree of maturation of encapsulation has reached anacceptable level to permit the use of impedance-based detectiontechniques. Briefly, impedance-based parameters such as CI or PE signalsare detected following device implant. The degree of maturation ofencapsulation of components of the implanted device is assessed usingthe impedance-based parameters. The device then determines whether thedegree of maturation has reached an acceptable level and, if so,impedance-based device functions are controlled or activated in responsethereto. The impedance-based functions that are activated can be, forexample, impedance-based HF/PE detection systems or procedures. In thismanner, the impedance-based HF/PE detection systems of the implantabledevice can be activated as soon as encapsulation has matured, withoutnecessarily waiting until completion of the typical forty-five tosixty-day post-implant moratorium.

In an illustrative embodiment of the second aspect of the invention, theimplantable device has one or more electrode pairs subject toencapsulation effects. The degree of maturation of encapsulation of aparticular electrode pair is performed by determining an impedanceresponse for the electrodes as a function of frequency and thendetermining the degree of maturation of tissues surrounding theelectrodes based on the impedance frequency response. For example,changes in the magnitude or phase of impedance as a function offrequency can be assessed. The changes are then compared against lookuptables to identify the type of tissue surrounding the electrodes, whichmight be blood, thrombus, inflammatory tissue, myocardium, fibrosis orendothelium. The degree of maturation is then assessed based on the typeof encapsulating tissue. For example, if the tissue surrounding anelectrode is found to be subacute inflammatory tissue, thenencapsulation has not yet matured. Conversely, if the tissue surroundingthe electrode is found to be chronic fibrotic tissue, then encapsulationis deemed to have matured and the electrode can be reliably used todetect impedance signals for the purposes of detecting HF, cardiogenicPE or other cardiac decompensation events. In other examples, thematuration of encapsulation is instead assessed based on the degree ofstability of the impedance signals, with greater stability beingassociated with a greater degree of encapsulation maturity. Stillfurther, in some examples, the thickness of overgrowth tissuesencapsulating the electrodes can be assessed.

Depending upon the particular embodiment, the impedance-based parametersused to assess the maturity of encapsulation are measured by applyingimpedance detection pulses between selected electrode pairs or byapplying low-level high-frequency alternating current (AC) signals. Ineither case, a voltage signal representative of impedance is thenmeasured using a selected electrode pair or another pair of electrodescoupled to the device. The voltage signal is then used to obtain phaseand amplitude impedance information.

To assess the maturity of encapsulation of the implantable deviceitself, the housing of the device can be equipped with two or more“device can” electrodes, which are employed as an electrode pair forassessing encapsulation effects in the device pocket. Further, thesimilarity or difference in impedance signal between the can and each oftwo or more distant and/or large electrodes (for example, can-to-RV coiland can-to-SVC coil) may be employed to ascertain the maturity ofencapsulation in the device pocket. Still further, the device can beequipped with various internal physiological sensors—such as acousticsensors or 3D accelerometers—that can be used to assess the degree ofmaturation of encapsulation of the device housing based on frequencybandwidths of detected signals. For example, the frequency bandwidth ofheart sounds or respiration sounds detected by an acoustic sensor can beused to assess the type of tissue in the device pocket.

System, apparatus and method examples of these and other techniques aredescribed below.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and further features, advantages and benefits of the inventionwill be apparent upon consideration of the descriptions herein taken inconjunction with the accompanying drawings, in which:

FIG. 1 illustrates pertinent components of an implantable medical systemhaving a pacer/ICD/CRT device equipped with encapsulation-responsiveacute phase HF/PE detection systems;

FIG. 2 provides an overview of a method performed by the system of FIG.1 for detecting HF/PE using non-impedance-based parameters during theacute phase;

FIG. 3 provides an exemplary graph illustrating changes in variousimpedance vectors occurring during the acute phase that might otherwiseprevent the detection of HF/PE during the acute interval without thetechniques of FIG. 2;

FIG. 4 illustrates an exemplary embodiment of the technique of FIG. 2wherein HRV, ventricular ER and other non-impedance-based parameters areused to detect HF/PE during the acute phase;

FIG. 5 includes exemplary graphs illustrating changes in ventricular ERand AV/PV delays that can be exploited by the technique of FIG. 4 todetect HF/PE;

FIG. 6 includes an exemplary graph illustrating an ER T-wave minparameter that can be exploited by the technique of FIG. 4 to detectHF/PE;

FIG. 7 provides an overview of a method performed by the system of FIG.1 for activating an impedance-based HF/PE detection system based on thedegree of maturation of component encapsulation;

FIG. 8 includes an exemplary graph illustrating changes in the magnitudeof impedance signals following device implant that can be exploited bythe technique of FIG. 7 to detect maturation of encapsulation based onimpedance stability;

FIG. 9 illustrates an exemplary embodiment of the technique of FIG. 7wherein frequency response used to determine the degree of maturation ofelectrode pairs;

FIG. 10 includes exemplary graphs illustrating changes in impedanceamplitude and phase as a function of frequency for fibrotic andthrombotic tissues that can be exploited by the technique of FIG. 9;

FIG. 11 includes exemplary graphs illustrating changes in impedance as afunction of overgrowth thickness for fibrotic and thrombotic tissuesthat can be exploited by the technique of FIG. 9;

FIG. 12 illustrates an exemplary embodiment of the technique of FIG. 7wherein the maturation of the device pocket is assessed based onimpedance as measured by a pair of device housing electrodes;

FIG. 13 illustrates a pair of device housing “can” electrodes that canbe exploited using the technique of FIG. 12 to assess the maturation ofthe device pocket;

FIG. 14 illustrates an exemplary embodiment of the technique of FIG. 7wherein the maturation of the device pocket is assessed based onphysiological sensor signals such as heart sounds;

FIG. 15 is a simplified, partly cutaway view, illustrating thepacer/ICD/CRT of FIG. 1 along with a more complete set of exemplaryleads implanted in the heart of a patient;

FIG. 16 is a functional block diagram of the pacer/ICD/CRT of FIG. 15,illustrating basic device circuit elements that provide cardioversion,defibrillation and/or pacing stimulation in four chambers of the heartand particularly illustrating components within the device forperforming or controlling the techniques of FIGS. 2-14; and

FIG. 17 is a functional block diagram illustrating components of adevice programmer and in particular illustrating programmer-basedcomponents for performing or controlling the techniques of FIGS. 2-14based on data sent from the implanted device.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The following description includes the best mode presently contemplatedfor practicing the invention. This description is not to be taken in alimiting sense but is made merely to describe general principles of theinvention. The scope of the invention should be ascertained withreference to the issued claims. In the description of the invention thatfollows, like numerals or reference designators are used to refer tolike parts or elements throughout.

Overview of Implantable Medical System

FIG. 1 illustrates an implantable medical system 8 having a pacemaker,ICD, or CRT device 10 (herein “pacer/ICD”) equipped with acute phaseHF/PE detection systems operative to detect cardiac decompensationevents such as HF and cardiogenic PE during an initial acute phasefollowing device implant using impedance or other electrical signalsmeasured via a set of cardiac pacing/sensing leads 12 or using variousphysiological sensors. A stylized representation of two cardiacpacing/sensing leads is provided In FIG. 1. A more complete illustrationof a set of leads is provided in FIG. 15, discussed below. In oneexample of the operation of the device, various non-impedance-basedparameters, such as HRV and ER, are employed during the acute phase todetect the onset or progression of HF, PE or other medical conditions.In another example, impedance and/or physiological signals are used toassess the maturity of encapsulation of the electrodes to determinewhether impedance-based HF/PE detection systems or algorithms can beactivated during what would otherwise be regarded as the acute phase.One such algorithm is a pulmonary congestion monitoring algorithm calledCorVue™. CorVue™ allows for the continuous monitoring of pulmonary fluidretention.

Upon detection of a cardiac decompensation event, warning signals may begenerated, diagnostic information stored and/or therapy delivered.Warning signals may be generated using either a warning device internalto pacer/ICD 10 or using an external bedside monitor 14. The internalwarning device may be a vibrating device or a “tickle” voltage devicethat, in either case, provides perceptible stimulation to the patient toalert the patient so that the patient may consult a physician. In oneexample, once the tickle warning is felt, the patient positions anexternal handheld device above his or her chest, such as a personaladvisory module (PAM), not separately shown. The handheld devicereceives short-range telemetry signals from the implanted device andprovides audible or visual verification of the warning signal. Thehandheld warning device thereby provides confirmation of the warning tothe patient, who might be otherwise uncertain as to the reason for theinternally generated warning signal. For further information regardingthis type of warning/notification technique, see U.S. Pat. No. 7,272,436to Gil et al.

If a bedside monitor is provided, the bedside monitor provides audibleor visual alarm signals to alert the patient as well as textual orgraphic displays. In addition, diagnostic information pertaining toheart failure is transferred to the bedside monitor or is stored withinthe pacer/ICD for subsequent transmission to an external programmer (seeFIG. 17) for review by a physician or other medical professional.External programmers are typically used during follow-up sessions withthe patient wherein a clinician downloads information from the implanteddevice, reviews the information and then adjusts the control parametersof the implanted device, if needed, via the programmer. Bedside monitorstypically download information more frequently, such as once perevening, and can be equipped to relay the most pertinent information tothe patient's physician via a communication network. In any case, thephysician may then prescribe any other appropriate therapies to addressthe condition. The physician may also adjust the operation of thepacer/ICD to activate, deactivate or otherwise control any therapiesthat are automatically applied. The bedside monitor may be directlynetworked with a centralized computing system, such as the HouseCall™system or the Merlin.Net system of St. Jude Medical, for immediatelynotifying the physician of any significant increase in LAP. Networkingtechniques for use with implantable medical systems are set forth, forexample, in U.S. Pat. No. 6,249,705 to Snell, entitled “DistributedNetwork System for Use with Implantable Medical Devices.”

Upon detection of a cardiac decompensation event, various forms oftherapy may be activated, adjusted or otherwise controlled by thepacer/ICD. If the implanted system is equipped with a drug pump 16,appropriate medications may be automatically administered to address thedecompensation. Alternatively, if a drug pump is not available, thepatient may be provided with instructions via the bedside monitor as towhat dosage to take for various heart failure medications. Exemplaryheart failure medications include angiotensin-converting enzyme (ACE)inhibitors such as captopril, enalapril, lisinopril and quinapril,diuretics, digitalis, nitrates, and other compounds. Depending upon theparticular medication, alternative compounds (e.g., intravenous orsubcutaneous agents) may be required for use in connection with animplantable drug pump. Routine experimentation may be employed toidentify medications for treatment of heart failure or other conditionsthat are safe and effective for use in connection with an implantabledrug pump. Dosages may be titrated based upon the severity ofdecompensation. Various techniques may be employed to confirm thedetection of heart failure (or other medical conditions) made by thepacer/ICD before warnings are generated or any therapy is delivered.

If so equipped, CRT therapy or other forms of electrical cardiac rhythmmanagement therapy may be initiated and controlled by the pacer/ICD. CRTand related therapies are discussed in, for example, U.S. Pat. No.6,643,546 to Mathis et al., entitled “Multi-Electrode Apparatus andMethod for Treatment of Congestive Heart Failure”; U.S. Pat. No.6,628,988 to Kramer et al., entitled “Apparatus and Method for Reversalof Myocardial Remodeling with Electrical Stimulation”; and U.S. Pat. No.6,512,952 to Stahmann et al., entitled “Method and Apparatus forMaintaining Synchronized Pacing”. CRT parameters may be adaptivelyadjusted by the device to improve the effectiveness of CRT usingtechniques set forth in the Panescu et al. patent application,“Closed-Loop Adaptive Adjustment of Pacing Therapy based on CardiogenicImpedance Signals Detected by an Implantable Medical Device,” citedabove. See, also, U.S. Patent Application 2009/0254140 of Rosenberg etal., entitled “Cardiac Resynchronization Therapy Optimization usingParameter Estimation from Realtime Electrode Motion Tracking,” andrelated patent applications. Still further, see, U.S. Patent Application2010/0152801 of Koh et al., “Cardiac Resynchronization TherapyOptimization Using Vector Measurements Obtained from Realtime ElectrodePosition Tracking,” and related patent applications.

Additionally, the pacer/ICD performs various standard operations, suchas delivering demand based atrial or ventricular pacing, overdrivepacing therapy, or antitachycardia pacing (ATP). The pacer/ICD alsomonitors for ventricular fibrillation and delivers defibrillation shocksin response thereto.

Hence, FIG. 1 provides an overview of an implantable medical systemcapable of: detecting HF or other conditions during the acute phasefollowing device implant (as well as during the subsequent chronicphase); delivering any appropriate warning/notification signals; andselectively delivering medications, when warranted. Embodiments may beimplemented that do not necessarily perform all of these functions. Forexample, embodiments may be implemented that detect cardiacdecompensation but do not automatically initiate or adjust therapy.Moreover, systems provided in accordance with the invention need notinclude all of the components shown in FIG. 1. In many cases, the systemwill include only a pacemaker, ICD, CRT and its respective leads.Warning devices and drug pumps are not necessarily implanted. These arejust a few exemplary embodiments. No attempt is made herein to describeall possible combinations of components that may be provided inaccordance with the general principles of the invention.

In addition, note that the particular locations of the implantedcomponents shown in FIG. 1 are stylized and may not necessarilycorrespond to actual implant locations. Although internal signaltransmission lines provided are illustrated in FIG. 1 forinterconnecting the various implanted components, wireless signaltransmission may alternatively be employed.

HF/PE Detection During Acute Phase Using Non-Impedance Signals

FIG. 2 provides a broad overview of techniques that may be performed fordetecting cardiac decompensation during the acute phase. Beginning atstep 100, a pacer/ICD is implanted within a patient along with a set ofleads incorporating electrodes or other components sensitive to tissueencapsulation. Otherwise conventional techniques may be employed toimplant the device and its leads. At step 102, during an acute phase orinterval following device implant, the pacer/ICD detects HF, PE or othercardiac decompensation events within the patient using one or moredetection signals that are relatively insensitive to componentencapsulation effects, such as HRV parameters, ventricular ER parametersor other non-impedance-based detection signals or parameters. Herein,the acute phase is generally regarded as the interval between deviceimplant and the point in time when components used for detectingimpedance have been properly encapsulated by mature tissues. This isoften deemed to take about forty-five days. However, as will beexplained in greater detail below, different components may beencapsulated sooner, or in some cases, later than this forty-five dayinterval. Techniques for detecting the end of acute phase for particularcomponents are described below.

At step 104, following the post-implant acute interval, the pacer/ICDdetects possible HF, PE other cardiac decompensation events within thepatient using one or more detection signals that are relatively moresensitive to component encapsulation effects, such as transthoracicimpedance (PE) signals or intracardiac impedance (CI) signals.Additionally, as will be described, these impedance signals can besupplemented with non-impedance-based signals of the type used duringthe acute phase so as to improve the specificity and reliability ofevent detection.

At step 106, based on the detection of any cardiac decompensation eventswithin the patient, the pacer/ICD generates warnings, recordsdiagnostics, titrates medications and/or controls other forms oftherapy, as already mentioned.

FIG. 3 provides an exemplary graph 108 illustrating changes in varioustransthoracic (i.e. PE) impedance vectors occurring during thepost-implant acute phase 108, which may end about forty-five days afterimplant, as indicated by vertical line 110. As can be seen, during theacute phase, the impedance signals vary significantly. During thesubsequent chronic phase, the signals are much more stable. Note that,in this example, even during the chronic phase, some of thetransthoracic impedance signals decrease over time, indicative of apossible increase in pulmonary congestion in this particular patient orother physiologic changes. Such increases in pulmonary congestion may bedue to pneumonia. Other factors that may affect thoracic impedance areblood/fluid partitioning (i.e., the amount of blood in arteries versusveins, or the amount of plasma in blood versus that in theinterstitial), the osmolarity of plasma and interstitial fluids (thebalance of which may be affected by drugs, diet, or other conditions),or geometric factors (e.g. if the patient loses weight, the device canmay be closer to the leads than before).

FIG. 4 provides a detailed example of the general technique of FIG. 2wherein HRV, ventricular ER and other non-impedance-based parameters areused to detect HF/PE during the acute phase. Beginning at step 200, thepacer/ICD is implanted along with its leads. At step 202, the devicedetects one or more non-impedance-based parameters such as: HRVparameters; ventricular ER parameters; paced or sensed AV/PV delayparameters; and paced or sensed VV delay parameters. Exemplary AV and VVfeatures that can be employed are sensed AV delay, paced AV delay, LVpaced RV sense delay, and RV paced LV sense delay. Insofar as AV/PVdelay parameters are concerned, it is noted that, advantageously, the AVdelay (versus the PV delay) may not require correction for ratedependence since tests can be run at a fixed heart rate (A pacing).However, PV parameters including PV delay or PV delay variability (morestrictly speaking, PR delay and PR variability) can be used to measureatrioventricular conduction and sympathetic/parasympathetic balance,respectively.

Exemplary ER features that can be used include: a peak-to-peak amplitudeduring a ventricular paced depolarization window (wherein “paceddepolarization” refers to the portion of the paced ER waveform that isanalogous to the QRS-complex within intrinsic cardiac beats); a paceddepolarization integral (PDI); a maximum slope (or slew rate) during thepaced depolarization window; and an ER T-wave minimum (wherein “ERT-wave” refers to the portion of the paced ER waveform that correspondsto repolarization within intrinsic cardiac beats.) U.S. Pat. No.6,473,647 to Bradley et al. discusses using ER features, especially achange in the ER feature with respect to the progression of heartdisease. See, also, U.S. Pat. No. 7,440,804 to Min et al., entitled“System and Method for Measuring Ventricular Evoked Response using anImplantable Medical Device,” which discusses analyzing ER features todetect HF, and U.S. Pat. No. 7,430,447, also of Min et al., entitled“Evoked Response and Impedance Measures for Monitoring Heart Failure andRespiration.” PDI is discussed in U.S. Pat. No. 5,643,327 to Dawson etal. Otherwise routine experimentation can be used to identify particularER or AV/PV/VV features or combinations of features to achieve preferredor optimal algorithms for detecting decompensation events.

Insofar as HRV is concerned, U.S. Pat. No. 6,480,733 to Turcott,entitled “Method for Monitoring Heart Failure,” discusses the use of HRVin detecting HF. As noted therein, significant excursions in HRV areindicative of HF exacerbation. Particularly effective techniques formeasuring and quantifying HRV are described, for example, in U.S. patentapplication Ser. No. 12/558,385, filed Sep. 11, 2009, of Bharmi et al.,entitled “System and Method for use with an Implantable Medical Devicefor Detecting Stroke based on Physiological and Electrocardiac Indices.”

Typically, the various AV/VV and ER parameters, as well as HRV values,are detected within—or are derived from—intracardiac electrogram (IEGM)signals detected using the various electrodes of the leads. Note thatthese IEGM signals are not significantly affected by encapsulationaffects and hence can be reliably used during the acute phase.

At step 204, the device also detects one or more of: patient posture;patient activity; blood pressure, which can be used to corroborate orsupplement the signals and parameters detected at step 202. Techniquesfor detecting patient posture or changes in posture are set forth inU.S. Pat. No. 7,149,579 to Koh et al., entitled “System and Method forDetermining Patient Posture Based On 3-D Trajectory Using an ImplantableMedical Device”. Patient activity can be detected using an activitysensor or activity variance sensor. Any of a variety of techniques canbe used to detect blood pressure. Examples are described in U.S. patentapplication Ser. No. 11/378,604, filed Mar. 16, 2006, of Kroll et al.,entitled “System and Method for Detecting Arterial Blood Pressure basedon Aortic Electrical Resistance using an Implantable Medical Device.”

At step 206, the device detects a possible HF or PE event during theacute phase using HRV, ventricular ER, AV/PV delay and/or VV delay orother non-impedance-based parameters, supplemented by patient posture,activity or blood pressure signals. In this regard, it is known thatAV/VV delays and ER features correlate very well with LAP during rapidpacing-induced cardiac decompensation events in canine test subjects.That is, changes in AV/VV delays and ER features correlate with changesin LAP, which correlate with HF and cardiogenic PE. Hence, changes inAV/VV delays can be used to detect an indication of HF and cardiogenicPE. Also, at step 206, the device responds to the detecteddecompensation event by, as already explained, generating warnings,titrating medications, delivering therapy, etc. Note also that thedevice might employ filtering windows or moving average windows tocollect and process the non-impedance-based parameters. The duration ofthese windows can begin at one length and then increase as the acutephase proceeds. For example, an averaging window might be set initiallyto five days (so as to permit HF detection beginning only five daysafter implant) and then might expand up to fourteen days as more data iscollected. In particular, a system of graded alerts or graded thresholdsmay be applied during the period with shortened windows. For example,since a “detection” with only five days of data may not be as specificas a detection with fourteen days of data, the alert may be worded moresoftly, or alternately the threshold to issue an alert or therapy basedon only five days would be higher than that to issue alert/therapy basedon a longer period.

FIG. 5 illustrates ER and AV/VV measurements. More specifically, graph208 illustrates a correlation (inverse, in this case) between an ERfeature and LAP. (More specifically, the plotted ER feature is PDI; theunits on the vertical axis are mV*ms.) Three rounds of rapid pacing wereperformed at times 209 to induce decompensation events within a caninetest subject and corresponding increases in LAP by as much as 20 mmHg.As can be seen, the ER feature 210 is inversely correlated with LAP 212,such that a sharp decrease in ER can be used to indicate a sharpincrease in LAP, which is indicative of a cardiac decompensation event.(Note that LAP was not measured throughout the entire duration of thegraph and hence there is gap in the LAP data.) Graph 214 illustrates acorrelation (direct, in this case) between an AV/VV feature and LAP.(The AV/VV feature plotted relates to the aforementioned AV/VV delays.More specifically, the plotted feature is LV pace to RV sense time,expressed in ms.) Three rounds of rapid pacing were performed at times215 to induce decompensation events and corresponding increases in LAP.As can be seen, the AV/VV feature 216 is correlated with LAP 218, suchthat a sharp increase in the AV/VV feature can be used to indicate asharp increase in LAP, which is indicative of a cardiac decompensationevent.

FIG. 6 illustrates the ER T-wave min feature (also referred to herein asthe “paced T-wave min”) that can be used as one of the non-impedancebased parameters at step 206 of FIG. 4. More specifically, graph 220illustrates a paced depolarization window 222 in which a paceddepolarization event 224 is detected. The graph also illustrates a pacedT-wave window 226 in which an ER T-wave 228 is detected. The ER T-waveminimum 230 is measured with respect to a baseline level 232. Note thatU.S. Pat. No. 7,072,715 to Bradley, entitled “Implantable CardiacStimulation Device for and Method of Monitoring Progression orRegression of Heart Disease by Monitoring Evoked Response Features”discusses the use of the ER T-wave, particularly T-wave slew rate andT-wave amplitude, for tracking HF. See, also, U.S. Pat. No. 7,676,264 toPillai et al., entitled “Systems and Methods for use by an ImplantableMedical Device for Evaluating Ventricular Dyssynchrony based on T-waveMorphology.”

Returning to step 206 of FIG. 4, insofar as supplementing the detectionof HF/PE with patient posture, activity or blood pressure, theseparameters can be used to help avoid false HF detections that might betriggered by changes in posture or patient activity, including activitytriggering increases in blood pressure. That is, if HF is indicatedbased on the aforementioned non-impedance-based parameters, but thatindication coincides with significant changes in posture or activity,then the device preferably collects and analyzes additional data beforetaking action in response to the HF event. This represents just onepossible way to interpret sensor-related changes in the context ofadditional data on posture and/or activity. An alternativeinterpretation is to “bin” sensor data such that there are multipletrends stored and updated, corresponding each to one set of posture oractivity data. See, generally, U.S. Pat. No. 7,336,999 to Koh, entitled“Means to Check the Validity of Heart Failure Surrogate Parameters fromEvoked Response using 3-D Accelerometer Queue.”

At step 234, the implanted device detects the end of the acute phasebased on the expiration of predetermined time period (such as forty-fivedays or sixty days) or based on other factors such as impedance signalstability. In one particular example, a sixty-day interval is employedwhich is based on a forty-five day post-implant moratorium plus atwo-week impedance data collection averaging interval. In anotherexample, a forty-five-day interval is employed which is based on athirty day post-implant moratorium plus a two-week impedance datacollection averaging interval. As such, these intervals are merelyexemplary and other durations can be selected. Insofar as assessingimpedance stability is concerned, the device tracks changes in impedanceoccurring during the acute phase (see, again, FIG. 3) to detect whenthose changes stabilize (by, for example, comparing a parameterrepresentative of impedance variation against a threshold indicative ofstabilization.) Note that the non-impedance-based parameters can be usedto corroborate or supplement the determination that impedance signalshave stabilized. For example, referring again to FIG. 3, about thirtydays after implant, several of the transthoracic (PE) impedance vectorsappear to level off. If the impedance values are deemed to be level bythe device, and the ER, AV/VV, and HRV features indicate that thepatient is stable during the same period, the device can then concludethat the corresponding electrodes have matured so that impedance-basedHF/PE detection can be invoked. On the other hand, if the impedancevectors appear to be level but the non-impedance features indicate thatthe patient is transitioning (e.g. HF worsening) then the “apparent”stability of impedance vectors are deemed to be false and a full sixtydays should be allowed for maturation (or forty-five days in exampleswhere a shorter moratorium is used.) Thus, an apparent stabilization ofPE/CI signals that is corroborated by stable ER, AV/VV, HRV, and/orother sensors can enable early termination of the maturation period andentry into the full impedance-based HF/PE monitoring algorithm.Additionally or alternatively, the device can exploit the techniquesdiscussed below with reference to FIGS. 7-14 to detect the maturation ofencapsulation. Note also that there can be fluctuations on the impedancetrend depending upon how frequently data is collected. For FIG. 3, datawas collected every two hours. In contrast, FIG. 8 (discussed below)illustrates impedance data collected only once a day and hence the dataof FIG. 8 appears more stable.

Continuing with FIG. 4, assuming the patient is still within the acutephase, processing returns after step 234 to steps 202 and 204 forfurther acute interval processing. Once the acute phase has ended,processing continues to step 236 wherein the device immediately orgradually activates its impedance-based HF/PE detection systems todetect possible HF/PE events during the ensuing chronic phase based onimpedance. Note that, rather than detecting impedance, other relatedelectrical signals or parameters can instead be exploited, such asadmittance, conductance, immittance or their equivalents. Generally,herein, “impedance signals” or “impedance parameters” broadlyencompasses impedance and/or any of these electrical equivalents andthose skilled in the art can readily convert one such parameter intoanother. Note also that the impedance-based detection of step 236 may beperformed either alone or in combination with various of thenon-impedance based parameters already discussed, such as HRV andventricular ER. That is, non-impedance-based detection parameters can beused to corroborate or supplement any HF/PE detection made based onimpedance signals.

The impedance-based HF/PE detection performed at step 236 can exploittechniques of the various patent documents cited above, such as those byBornzin et al., Min et al, Panescu et al., and Wenzel et al. See, also,techniques described in U.S. patent application Ser. No. 11/559,235,entitled “System and Method for Estimating Cardiac Pressure UsingParameters Derived from Impedance Signals Detected by an ImplantableMedical Device,” and also techniques described in the followingapplications: U.S. Provisional Patent Application No. 60/787,884entitled “Tissue Characterization Using Intracardiac Impedances with anImplantable Lead System” and in U.S. patent application Ser. Nos.11/558,101; 11/557,851; 11/557,870; 11/557,882; and 11/558,088, eachentitled “Systems and Methods to Monitor and Treat Heart FailureConditions.”

Insofar as non-impendence-based corroboration is concerned, an HFdetection parameter can be generated that combines impedance-basedindicators with non-impedance-based indicators for comparison againstone or more thresholds indicative of a cardiac decompensation event.See, for example, the graded alerts or graded thresholds discussedabove. The relative weights given the impedance-based parameters vs. thenon-impedance-based parameters can vary gradually as the acute intervalcomes to an end. For example, upon completion of the acute phase, theweight applied to impedance-based signals can be gradually increaseduntil reaching some preferred weight for use during the chronic phase.An impedance averaging window or a filtering window can be used thatincreases in duration up to some preferred length for use during thechronic phase. Note that the particular non-impedance-based parametersused during the chronic phase might differ from those used during theacute phase. Likewise, any particular thresholds used for detectingHF/PE can differ during the chronic phase as compared to the acutephase. Furthermore, thresholds used during the lead maturation or afterlead maturation can be manually set by a clinician or other user. Insome implementations, these different thresholds are automaticallydetermined by the device. When the device sets the thresholds, they canbe fixed thresholds or patient-specific thresholds. Insofar as ER-basedcorroboration is concerned, see, e.g., U.S. Patent Application2005/0216067 of Min et al., “System and Method for Predicting a HeartCondition based on Impedance Values using an Implantable MedicalDevice,” which discusses techniques wherein ER features are exploited tocorroborate the HF predictions.

Thus, FIGS. 2-6 illustrate exemplary techniques for detecting cardiacdecompensation events during the initial acute phase using non-impedancebased parameters. In the following section, techniques for earlyactivation of impedance-based detection systems are described.

Maturation-Based Activation of Impedance-Based HF/PE Detection Systems

FIG. 7 summarizes techniques for activating impedance-based HF/PEdetection systems based on a degree of maturation of componentencapsulation as detected by the implanted device. Beginning at step300, the pacer/ICD is implanted within a patient along with a set ofleads that incorporate electrodes or other components sensitive totissue encapsulation. At step 302, the device detects impedance-basedsignals following implant of the device such as transthoracic (PE) orcardiogenic impedance (CI) parameters. At step 304, the device assessesthe degree of maturation of encapsulation of components of the implanteddevice using the impedance-based signals. Exemplary techniques will bedescribed in detail below that assess the type of tissue surroundingparticular electrodes and the thickness thereof. At step 306, the devicedetermines whether the degree of maturation has reached an acceptablelevel, such as a level ensuring stability of the impedance signals.Then, at step 308, based on whether the degree of maturation has reachedthe acceptable level, the device controls or activates itsimpedance-based HF/PE detection systems to detect possible cardiacdecompensation events within the patient and/or to control other devicefunctions in response thereto. Prior to this point in time, the devicecan instead use the aforementioned non-impedance-based parameters todetect HF/PE. Any of the various transitioning techniques discussedabove, where relative weights are adjusted or where the durations offiltering windows are selectively varied, can be used as well, totransition from one detection technique to another. Insofar ascontrolling device functions is concerned, it should be understood thatany function that the pacer/ICD can perform or control, alone or incombination with other devices, is a “device function.” The term“controlling” broadly encompasses any of a variety of control functions,such as activating device components/procedures, deactivating devicecomponents/procedures, adjusting device components/procedures, etc.

FIG. 8 provides an exemplary graph 310 illustrating changes intransthoracic (i.e. PE) impedance vectors occurring post-implant,particularly an LV bipolar impedance vector 312 and an RV bipolarimpedance vector 324. In this example, during the first ten or so daysfollowing implant, the LV bipolar impedance changes significantly, thenstabilizes. The RV bipolar impedance stabilizes after about twenty days.As such, both stabilize well in advance of the typical forty-five dayimpedance-detection moratorium discussed above. With the technique ofFIG. 7, this early stabilization is detected to permit early use ofimpedance-based HF/PE detection systems.

FIG. 9 provides an example of the general technique of FIG. 7 whereinfrequency response is used to assess the particular type of tissuesurrounding electrodes, as well as its thickness. Beginning at step 400,the pacemaker, ICD, CRT or other medical device is implanted along withits leads. At step 402, the device applies impedance detection pulses orlow-level high frequency AC currents to patient tissues using variouselectrode pairs and, for each pair, measures voltage signals in responsethereto to calculate impedance.

A particularly effective tri-phasic impedance detection pulse for use indetecting impedance is described in U.S. patent application Ser. No.11/558,194 of Panescu et al., filed Nov. 9, 2006, entitled “Closed-LoopAdaptive Adjustment of Pacing Therapy based on Cardiogenic ImpedanceSignals Detected by an Implantable Medical Device.” The tri-phasicwaveform is a frequency-rich, low energy waveform that provides anet-zero charge and a net-zero voltage. However, other impedancedetection pulses or waveforms may instead be exploited. Insofar as thelow-level, high-frequency AC current is concerned, this current isdriven across an electrode pair and then the voltage across the same oranother electrode pair is measured to determine an impedance value. Forexample, 16 Hz for PE, 128 Hz for CI measurements. In general, theimpedance value will have real and imaginary parts, which can beconsidered mathematically as an amplitude and phase components. Severalfrequencies of current are driven (at the same or different times) andthe resultant voltages are measured to generate plots of impedance(amplitude or phase) versus frequency (wherein the plots are storedinternally within the memory systems of the device using suitable datarepresentations.)

To distinguish between different possible tissues, a wide frequencyrange should be tested, for example from direct current (DC) or 0.1 Hzup to 10 MHz-100 MHz. This range need not be sampled completely noruniformly, and in fact it may be advantageous to take only 1 or 2frequency samples in each decade (i.e. logarithmic sampling).Alternately, it may be possible to drive current such as white noise orpink noise, and measure the spectral response. Insofar as the amplitudeis concerned, a typical requirement is that current density remainsbelow the capture threshold of cardiac tissue (or muscle tissue in thedevice pocket). For example, in a typical implantable system, 1-10 uAshould not capture cardiac tissue in the range approx >0.1 kHz

The impedance value measured using a given pair of electrodes is apair-based or vector-based impedance value that reflects the impedancesassociated with the pair of electrodes. As noted above, it is nowbelieved that the majority of the impedance characteristics occur withinabout one centimeter of measuring electrodes. That is, the measuredimpedance is dominated by the effects of near-field tissues rather thanfar-field tissues. As such, the impedance measured using a particularpair of electrodes represents the impedance near the first electrode ofthe pair combined with the impedance near the second electrode of thepair. Typically, about 80%-95% of the signal is within the near-field ofeither electrode, with the remaining 5-20% representing everything inbetween (blood, tissue, interstitial fluid, air, etc.) Note also that,the impact of cathode is typically much more important than anode. Forexample, a transthoracic (PE) impedance signal measured between the LVtip and the device housing primarily represents a combination of theimpedance near the LV tip and the impedance near the device itself, withcomparatively little contribution from the far-field between the twoelectrodes. Note though, that the far-field signal still has smallcontribution. Assuming that near-field signals (such as the LVtip andCan local impedance values) do not change significantly during pulmonaryedema, the small change in far-field then becomes the majordifferentiator. Hence, despite the relatively modest far-fieldcontribution, pulmonary fluid content can typically be detected based onchanges of ˜10% (e.g., a 50 Ohm drop on a 500 Ohm signal is certainlydetectable by the device impedance measurement circuitry). If thetissues around either of the two electrodes of the pair have not yetmatured, then the pair typically cannot be used to measure impedance forthe purposes of HF/PE detection. That is, it is not sufficient that justone of the electrodes of the pair has been encapsulated by maturetissues. Both of the electrodes of the measuring pair should be properlyencapsulated. Note also that, if the device measures several electricalvectors, it is typically feasible to discern the individual effects ofeach electrode using near-field-based techniques.

Techniques have been developed for determining the near-field impedanceassociated with an individual electrode, i.e. for isolating theimpedance associated with a particular electrode rather than a pair ofelectrodes. See, the near field-based impedance techniques described inU.S. patent application Ser. No. 12/853,130, filed Aug. 9, 2010, ofGutfinger et al., entitled “Near Field-based Systems and Methods forAssessing Impedance and Admittance for use with an Implantable MedicalDevice.” (Atty. Docket No. A10P1031.) These near field techniques mightbe useful in connection with the present invention to identifyencapsulating tissues on an electrode-by-electrode basis. However,unless otherwise noted, the impedance measurements employed by thetechniques described herein are vector-based or pair-based impedances,which reflect a combination of the impedances of the two electrodes ofthe voltage measuring pair.

At step 404, the device determines the impedance response as a functionof frequency for each pair of electrodes used to measure impedance basedeither on the magnitude or the phase of the impedance signal.

FIG. 10 illustrates exemplary impedance frequency response curves. Atfirst graph 406 provides two curves of impedance amplitude as a functionof frequency corresponding to different tissues encapsulating one orboth electrodes of the measuring pair. Curve 408 represents theamplitude-frequency response in the presence of fibrotic tissue. Curve410 represents the amplitude-frequency response in the presence ofthrombotic tissue. As can be seen, the frequency response is quitedifferent, permitting the device to distinguish the two types ofencapsulating tissue. At second graph 412 provides two curves ofimpedance phase as a function of frequency. Curve 414 represents thephase-frequency response in the presence of fibrotic tissue. Curve 416represents the phase-frequency response in the presence of thrombotictissue. Again, the frequency response is quite different. See, U.S.patent application Ser. No. 11/844,131 of Rosenberg et al., filed Aug.23, 2007, entitled “System and Method for In Vivo Sensor Recalibration”(Atty. Docket No. A07p1141), which describes the use of similarimpedance measurements at various frequencies for the purpose ofrecalibrating sensors.

The frequency response curves of FIG. 10 represent just a few examplesthat illustrate the differences in impedance response caused bydifferent encapsulating tissues. Additional frequency response curvescan be generated without undue experimentation for other types oftissues expected to encapsulate implantable electrodes during thematuration process, particularly blood, inflammatory tissue, myocardiumand endothelium. Lookup tables or templates are then stored within thememory of device so that the device can compare measured frequencyresponse curves with the stored data to identify the type of dataencapsulating the measuring electrodes. This is performed in the nextstep of FIG. 9.

Note that, in some cases, two or more different types of tissues mightencapsulate particular electrodes and so frequency-response curves canbe generated that account for the presence of a combination of differenttissues by, for example, using look-up tables. Alternatively,template-matching may be employed for the frequency response curves,such that only the tissue type most closely resembling the measuredresponse is identified. Yet another option is to employ a fuzzy-logicsystem that identifies the actual (probabilistic) contribution of eachencapsulating tissue type.

Likewise, in some cases, different types of tissues might encapsulatethe two electrodes of a given electrode pair (e.g. the LV tip electrodemight be encapsulated by one type of tissue, whereas the device housingmight be encapsulated by another type of tissue) and sofrequency-response curves are also preferably generated that account forsuch combinations. See, again, the near-field techniques of Gutfinger etal. cited above that can be used to isolate the contributions ofindividual electrodes. In some cases, due to the presence of too manydifferent types of encapsulating tissues, or for other reasons, it mightnot be feasible for the device to identify the particular tissuesassociated with a given pair of electrodes. In such circumstances,alternative techniques are used to assess the maturity of theencapsulating tissue, such as the impedance stabilization techniquesdiscussed below.

Note that frequency-response curves can be generated using eitherimpedance detection pulses or low-level high frequency AC currents orsome combination thereof. For example, the “frequency-rich triphasicpulse” may be tuned such that a small number of different pulses of thesame family cover the entire frequency range of interest. In the case ofimpedance pulses—so long as the pulse is sufficiently rich infrequencies—a suitable frequency response can be measured. See, e.g.,the frequency-rich tri-phasic pulse mentioned above.

Returning to FIG. 9, at step 418, for each pair of electrodes to beassessed, the device determines the degree of maturation of tissuesencapsulating the electrodes based on the impedance response by, e.g.,applying the impedance response values obtained at step 404 to look-uptables or templates representative of the particular type(s) oftissue(s) surrounding the electrodes—such as blood, thrombus,inflammatory tissue, myocardium, fibrosis, and endothelium—to determineif the electrodes are surrounded by mature tissues. In one example, ifthe tissue surrounding an electrode pair is found to be inflammatorytissue, then encapsulation has not yet matured. Conversely, if thetissue surrounding the electrode pair is found to be fibrotic tissue,then encapsulation is deemed to have matured. The particular type oftissue that is deemed to be mature tissue can vary depending uponelectrode type and location. For a ring electrode for implant within oneof the chambers of the heart or the coronary sinus, blood may beregarded as a mature “encapsulating” tissue. For an active-fixation tipelectrode for implant into the myocardium, myocardial tissue may beregarded as immature tissue since scar tissue has not yet formed aroundthe electrode. Additionally, at step 418, the device can assess thethickness of at least some types of tissues based on the amplitude ofthe measured impedance.

FIG. 11 illustrates impedance as a function of overgrowth thickness forthrombus and fibrosis. In a first region 420 of thickness, impedancedrops with increasing thickness. In a second region 422 of thickness,impedance does not change significantly. In the first region, impedancebegins dropping as thickness increases due to changes in the distancebetween the current source and the interface between encapsulatingtissue with blood. In the second region, the thickness of theencapsulating tissue is enough such that the tissue-blood interface haslittle to no effect on further impedance drops. This is the criterionfor a fully matured lead, at which point impedance-based HF/PEdiagnostics may be activated without significant risk of falsedetections. Note also that, in both regions, the type of tissue alsoaffects the impedance. Curve 424 corresponds to thrombus. Curve 426corresponds to fibrosis. As such, based on the measured impedance andthe known tissue type (determined from the frequency response), thedevice can assess the thickness of growth currently surrounding theelectrodes. The thickness can be used to assess maturity. For example,for a given electrode and for a given type of encapsulating tissue, athickness “region” threshold can be defined. If the thickness is foundto exceed that threshold, the encapsulation is deemed to be mature,since further increases in thickness are not likely to affect impedance.Note that, even if the tissue type is not known, using the time courseof impedance changes the device can match a template of a curve such as424 or 426. Alternatively, the device can set a threshold for the slopeof the curve, such that when the local impedance-versus-time curve is“flat enough” then the device can confidently conclude that theovergrowth thickness has reached a plateau.

Returning to FIG. 9, at step 418, the device additionally oralternatively assesses the degree of stability of the impedance signalsover time so as to determine the degree of maturity. In one example, abipolar pacing lead impedance is measured daily, such as LVtip-LVringand RVtip-RVcoil bipolar impedances. The average over several days isstored as a trend to determine stability. Note that the same bipolarpacing impedance vectors may be used to help determine the stability ofone or more transthoracic (PE) impedance vectors. For example, thepacing impedance for the RV bipolar can contribute to determination ofstability for RV-LV vector, RA-RV vector, RV-Case vector, etc.

Various specific mathematical methods can be used to determinestabilization. For example, comparison of current values or a short termaverages with a long-term average can be used to indicate a stableperiod if the current value does not differ from the average value, orit can indicate that the electrode is still in maturation period if thecurrent value does differ substantially from the average. As anotherexample, the change from a previous measurement to a current measurementcan be compared with the standard deviation of all previous measurements(or those during a pre-specified backward-looking window) and if thechange is small relative to the standard deviation then a stable periodis indicated. Conversely, if the change is large relative to thestandard deviation then an unstable maturation period is indicated.Other methods of determining stability are known as well. Such methodsmay be applied not only to the bipolar pacing impedance, but also to thetransthoracic (PE) impedance signals themselves. In particular, if onlyone or two signals mature differently than the others, there is higherprobability that this is due to differing tissue/lead maturation ratherthan an acute change in only one of the six measured PE vectors.

The stabilization determined by these methods can be used to flagimpedance vectors that are ready for use so the vectors can be used asthey become ready. For example, some devices record six PE impedancevectors but only rely on two (RVcoil-Case, LVring-Case) for calculationof a Pulmonary Fluid Index. It may be advantageous to have a modifiedFluid Index during the stabilization period that uses any or all of thesix (or other) impedance vectors (that have matured) until the time whenboth RVcoil-Case and LVring-Case have matured, at which point theconventional Fluid Index derived from those particular vectors is used.

At step 428, having determined the degree of maturation of encapsulatingtissues, the device then records diagnostic information representativeof the degree of maturation of tissue encapsulation, including tissuetype, overgrowth thickness, and an indication of whether a givenelectrode pair can be used for measuring impedance for the purposes ofHF/PE detection.

If the encapsulating tissue for the electrodes to be used forimpedance-based HF/PE detection is not yet mature, processing returns tostep 402 for further monitoring. Steps 402-428 of the figure may beperformed periodically or on demand. For example, serial measurementsare taken over hours, days, or up to a few weeks and the resulting trendis used to identify the onset of stability. Once at least one pair ofelectrodes (that are sufficient for impedance-based HF/PE detection)have matured, processing proceeds to step 430.

At step 430, the device then activates its impedance-based HF/PEdetection systems to detect HF/PE events or other cardiac decompensationevents using any or all stable electrode pairs. Additionally, eventhough impedance-based HF/PE detection systems have been activated thatrely on impedance detection pulses, the device can still applyadditional low-level high frequency AC signals to supplement the HF/PEdetection by, for example, using those signals to characterize thehealth of cardiac tissues. In this regard, it is likely that healthytissue and heart failure tissue will have different characteristicresponses to AC impedance. For example, it is known that ischemicmyocardium has a different response than non-ischemic myocardium;myocardial remodeling during heart failure progression includesreplacing some myocytes with fibrosis, even in the absence of ischemia.Thus, in at least some embodiments, the device utilizes thecharacteristic impedance response (amplitude and phase) of the tissue tobipolar AC impedance to track HF progression or otherwise contribute toa diagnosis of HF. This may be performed independently or in conjunctionwith the impedance measured via impedance detection pulses.

Thus, FIGS. 7-11 illustrate various techniques for assessing the degreeof maturity of electrodes or electrode pairs and for selectivelyactivating impedance-based HF/PE detection systems. These techniques areapplicable to a wide variety of leads and electrode pairs. In thefollowing, a specific example is described wherein the technique isapplied to the device housing.

FIG. 12 summarizes a technique wherein the maturation of the devicepocket is assessed based on impedance using a pair of electrodes coupledto the device can. Many of the steps of this technique have alreadydescribed above and hence will not be discussed again in detail.Briefly, at step 500, a pacemaker, ICD or CRT that has at least twodevice housing electrodes is implanted. FIG. 13 illustrates a pair ofdevice housing “can” electrodes 502 and 504 of a device housing 506 thatcan be exploited to assess the maturation of the device pocket based onimpedance. At step 508 of FIG. 12, the device applies impedancedetection pulses or low-level high frequency AC signals using the pairof electrodes and measures voltage signals in response thereto tocalculate impedance. At step 510, the device determines impedanceresponse as a function of frequency for the device housing electrodesbased either on the magnitude or phase of the impedance signal. At step512, the device determines the degree of maturation of tissuesencapsulating the device housing by: applying the impedance responsevalues to look-up tables or templates representative of the particulartype of tissue surrounding the device and its thickness to determine ifthe device is surrounded by mature tissues; and/or by assessing thedegree of stability of the impedance signals over time. At step 514, thedevice records diagnostic information representative of the degree ofmaturation of the tissues encapsulating the device housing. Inparticular, the device can issue warning signals if the device pocket isnot maturing as expected, as might be due to an infection in the devicepocket. Then, at step 516, based on whether the degree of pocketmaturation has reached an acceptable level, the device activates anyimpedance-based HF/PE detection vectors that utilize the device housingelectrodes to detect possible HF/PE within the patient and/or controlother device functions.

FIG. 13 summarizes an alternative technique wherein the maturation ofthe device pocket is assessed based on physiological sensor signalsrather than impedance signals or AC current signals. Some of the stepsof this technique have already described above and hence will not bediscussed again in detail. Briefly, at step 550, a pacemaker, ICD or CRThaving an internal 3D accelerometer, acoustic sensor or other“physiological sensor” capable of measuring sounds/vibrations affectedby pocket maturation is implanted. FIG. 15, discussed below, illustratesexemplary physiological sensors. At step 552 of FIG. 12, the devicemeasures sounds and/or vibrations using the physiological sensor, suchas heart sounds or respiration sounds and the frequency band of thosesounds. It is believed that before pocket maturation, blood and fluid inthe pocket as well as the “looseness” of the device case will tend todamp out higher frequencies of sound. After maturation, the case isencapsulated in a stiffer substrate that allows higher frequency soundsto be transmitted. Hence, the frequency bandwidth of the detected soundsor vibrations can be used to assess device pocket maturity.

At step 554, the device then determines the degree of maturation oftissues encapsulating the device housing based on the sounds/vibrationsby, e.g., applying values representative of the magnitude and/orfrequency of the sounds/vibrations to look-up tables or templatesrepresentative of the particular type of tissue surrounding thehousing—such as blood, thrombus, inflammatory tissue, myocardium,fibrosis, and endothelium—and its thickness to determine if the devicepocket has matured. This may be performed using the same generaltechniques discussed above in connection with impedancefrequency-response analysis but applied to the acoustic signals andtheir frequency bandwidths. Alternatively, the stability of thephysiological signals is assessed over time. At step 556, the devicerecords diagnostic information representative of the degree ofmaturation of the tissues encapsulating the device housing and warns ifthe device pocket is not maturing as expected. Then, at step 558, basedon whether the degree of pocket maturation has reached an acceptablelevel, the device activates any impedance-based HF/PE detection vectorsthat utilize the device housing electrodes to detect possible HF/PEwithin the patient and/or to control other device functions. As notedabove, the similarity or difference in impedance signal between the canand each of two or more distant and/or large electrodes (for example,can-to-RV coil and can-to-SVC coil) may be employed to ascertain thematurity of encapsulation in the device pocket. That is, the device canutilize two or more vectors including the case and at least one otherelectrode, as well as a vector including the “other” electrodes in thosetwo or more vectors, to determine the near-field impedance at thecase/device pocket. Following that determination, the assessment ofmaturity is completed.

Thus various techniques have been described that exploit electricalsignals (impedance, AC current) or physiological signals (heart sounds,respiration sounds, vibrations, etc.) to assess encapsulation maturity.In some examples, these parameters are measured and compared only whilethe patient is at rest, for consistency. A sleep or circadian detectormay be used to identify appropriate periods of time to measure theimpedance values. In addition, posture detectors may be used todetermine when the patient is in a certain predetermined posture (suchas supine) so as to reduce or eliminate any variations in themeasurement of the electrical or physiological parameters that may bedue to changes in posture. See, e.g., posture detection techniquesdescribed in U.S. Pat. No. 6,658,292 of Kroll et al., entitled“Detection of Patient's Position and Activity Status Using 3DAccelerometer-Based Position Sensor.” See, also, U.S. Pat. No.7,149,579, cited above.

For the sake of completeness, a detailed description of an exemplarypacer/ICD/CRT device for performing or controlling the varioustechniques described above will now be provided. However, principles ofinvention may be implemented within other pacer/ICD/CRT implementationsor within other implantable devices. Furthermore, although examplesdescribed herein involve processing of the various signals by theimplanted device itself, some operations may be performed using anexternal device, such as a device programmer, computer server or otherexternal system. For example, recorded data may be transmitted to anexternal device, which processes the data to evaluate encapsulationmaturity based on impedance signals and/or to detect HF/PE during theacute phase based on non-impedance signals. Processing by the implanteddevice itself is preferred as that allows prompt detection of HF/PE andprompt activation of impedance-based HF/PE detection systems.

Exemplary Pacer/ICD

With reference to FIGS. 15 and 16, a description of an exemplarypacer/ICD will now be provided. FIG. 15 provides a simplified blockdiagram of the pacer/ICD, which is a dual-chamber stimulation devicecapable of treating both fast and slow arrhythmias with stimulationtherapy, including cardioversion, defibrillation, and pacingstimulation, and also capable of performing or controlling the steps andfunctions discussed above. To provide other atrial chamber pacingstimulation and sensing, pacer/ICD 10 is shown in electricalcommunication with a heart 612 by way of a left atrial lead 620 havingan atrial tip electrode 622 and an atrial ring electrode 623 implantedin the atrial appendage. Pacer/ICD 10 is also in electricalcommunication with the heart by way of a right ventricular lead 630having, in this embodiment, a ventricular tip electrode 632, a rightventricular ring electrode 634, a right ventricular (RV) coil electrode636, and a superior vena cava (SVC) coil electrode 638. Typically, theright ventricular lead 630 is transvenously inserted into the heart soas to place the RV coil electrode 636 in the right ventricular apex, andthe SVC coil electrode 638 in the superior vena cava. Accordingly, theright ventricular lead is capable of receiving cardiac signals, anddelivering stimulation in the form of pacing and shock therapy to theright ventricle.

To sense left atrial and ventricular cardiac signals and to provide leftchamber pacing therapy, pacer/ICD 10 is coupled to a CS lead 624designed for placement in the “CS region” via the CS os for positioninga distal electrode adjacent to the left ventricle and/or additionalelectrode(s) adjacent to the left atrium. As used herein, the phrase “CSregion” refers to the venous vasculature of the left ventricle,including any portion of the CS, great cardiac vein, left marginal vein,left posterior ventricular vein, middle cardiac vein, and/or smallcardiac vein or any other cardiac vein accessible by the CS.Accordingly, an exemplary CS lead 624 is designed to receive atrial andventricular cardiac signals and to deliver left ventricular pacingtherapy using at least a left ventricular tip electrode 626 and a LVring electrode 625, left atrial pacing therapy using at least a leftatrial ring electrode 627, and shocking therapy using at least a leftatrial coil electrode 628. With this configuration, biventricular pacingcan be performed. Although only three leads are shown in FIG. 15, itshould also be understood that additional leads (with one or morepacing, sensing and/or shocking electrodes) might be used and/oradditional electrodes might be provided on the leads already shown.

A simplified block diagram of internal components of pacer/ICD 10 isshown in FIG. 16. While a particular pacer/ICD is shown, this is forillustration purposes only, and one of skill in the art could readilyduplicate, eliminate or disable the appropriate circuitry in any desiredcombination to provide a device capable of treating the appropriatechamber(s) with cardioversion, defibrillation and pacing stimulation.The housing 640 for pacer/ICD 10, shown schematically in FIG. 16, isoften referred to as the “can”, “case” or “case electrode” and may beprogrammably selected to act as the return electrode for all “unipolar”modes. The housing 640 may further be used as a return electrode aloneor in combination with one or more of the coil electrodes, 628, 636 and638, for shocking purposes. In the alternative embodiment of FIG. 13,rather than using the device housing as a single can electrode, a pairof “can” or “case” electrodes are provided. In such an embodiment,additional case/case electrode terminals are provided, which are notshown in FIG. 16.

The housing 640 further includes a connector (not shown) having aplurality of terminals, 642, 643, 644, 645, 646, 648, 652, 654, 656 and658 (shown schematically and, for convenience, the names of theelectrodes to which they are connected are shown next to the terminals).As such, to achieve right atrial sensing and pacing, the connectorincludes at least a right atrial tip terminal (A_(R) TIP) 642 adaptedfor connection to the atrial tip electrode 622 and a right atrial ring(A_(R) RING) electrode 643 adapted for connection to right atrial ringelectrode 623. To achieve left chamber sensing, pacing and shocking, theconnector includes at least a left ventricular tip terminal (V_(L) TIP)644, a left ventricular ring terminal (V_(L) RING) 645, a left atrialring terminal (A_(L) RING) 646, and a left atrial shocking terminal(A_(L) COIL) 648, which are adapted for connection to the leftventricular ring electrode 626, the left atrial ring electrode 627, andthe left atrial coil electrode 628, respectively. To support rightchamber sensing, pacing and shocking, the connector further includes aright ventricular tip terminal (V_(R) TIP) 652, a right ventricular ringterminal (V_(R) RING) 654, a right ventricular shocking terminal (V_(R)COIL) 656, and an SVC shocking terminal (SVC COIL) 658, which areadapted for connection to the right ventricular tip electrode 632, rightventricular ring electrode 634, the V_(R) coil electrode 636, and theSVC coil electrode 638, respectively.

At the core of pacer/ICD 10 is a programmable microcontroller 660, whichcontrols the various modes of stimulation therapy. As is well known inthe art, the microcontroller 660 (also referred to herein as a controlunit) typically includes a microprocessor, or equivalent controlcircuitry, designed specifically for controlling the delivery ofstimulation therapy and may further include RAM or ROM memory, logic andtiming circuitry, state machine circuitry, and I/O circuitry. Typically,the microcontroller 660 includes the ability to process or monitor inputsignals (data) as controlled by a program code stored in a designatedblock of memory. The details of the design and operation of themicrocontroller 660 are not critical to the invention. Rather, anysuitable microcontroller 660 may be used that carries out the functionsdescribed herein. The use of microprocessor-based control circuits forperforming timing and data analysis functions are well known in the art.

As shown in FIG. 16, an atrial pulse generator 670 and a ventricularpulse generator 672 generate pacing stimulation pulses for delivery bythe right atrial lead 620, the right ventricular lead 630, and/or the CSlead 624 via an electrode configuration switch 674. It is understoodthat in order to provide stimulation therapy in each of the fourchambers of the heart, the atrial and ventricular pulse generators, 670and 672, may include dedicated, independent pulse generators,multiplexed pulse generators or shared pulse generators. The pulsegenerators, 670 and 672, are controlled by the microcontroller 660 viaappropriate control signals, 676 and 678, respectively, to trigger orinhibit the stimulation pulses. Additionally, a high frequency, lowlevel AC current circuit 671 is provided for generating theaforementioned AC currents used to assess encapsulation maturity.

The microcontroller 660 further includes timing control circuitry (notseparately shown) used to control the timing of such stimulation pulses(e.g., pacing rate, AV delay, atrial interconduction (inter-atrial)delay, or ventricular interconduction (V-V) delay, etc.) as well as tokeep track of the timing of refractory periods, blanking intervals,noise detection windows, evoked response windows, alert intervals,marker channel timing, etc., which is well known in the art. Switch 674includes a plurality of switches for connecting the desired electrodesto the appropriate I/O circuits, thereby providing complete electrodeprogrammability. Accordingly, the switch 674, in response to a controlsignal 680 from the microcontroller 660, determines the polarity of thestimulation pulses (e.g., unipolar, bipolar, combipolar, etc.) byselectively closing the appropriate combination of switches (not shown)as is known in the art.

Atrial sensing circuits 682 and ventricular sensing circuits 684 mayalso be selectively coupled to the right atrial lead 620, CS lead 624,and the right ventricular lead 630, through the switch 674 for detectingthe presence of cardiac activity in each of the four chambers of theheart. Accordingly, the atrial (ATR. SENSE) and ventricular (VTR. SENSE)sensing circuits, 682 and 684, may include dedicated sense amplifiers,multiplexed amplifiers or shared amplifiers. The switch 674 determinesthe “sensing polarity” of the cardiac signal by selectively closing theappropriate switches, as is also known in the art. In this way, theclinician may program the sensing polarity independent of thestimulation polarity. Each sensing circuit, 682 and 684, preferablyemploys one or more low power, precision amplifiers with programmablegain and/or automatic gain control, bandpass filtering, and a thresholddetection circuit, as known in the art, to selectively sense the cardiacsignal of interest. The automatic gain control enables pacer/ICD 10 todeal effectively with the difficult problem of sensing the low amplitudesignal characteristics of atrial or ventricular fibrillation. Theoutputs of the atrial and ventricular sensing circuits, 682 and 684, areconnected to the microcontroller 660 which, in turn, are able to triggeror inhibit the atrial and ventricular pulse generators, 670 and 672,respectively, in a demand fashion in response to the absence or presenceof cardiac activity in the appropriate chambers of the heart.

For arrhythmia detection, pacer/ICD 10 utilizes the atrial andventricular sensing circuits, 682 and 684, to sense cardiac signals todetermine whether a rhythm is physiologic or pathologic. As used in thissection, “sensing” is reserved for the noting of an electrical signal,and “detection” is the processing of these sensed signals and noting thepresence of an arrhythmia. The timing intervals between sensed events(e.g., AS, VS, and depolarization signals associated with fibrillationwhich are sometimes referred to as “F-waves” or “Fib-waves”) are thenclassified by the microcontroller 660 by comparing them to a predefinedrate zone limit (i.e., bradycardia, normal, atrial tachycardia, atrialfibrillation, low rate VT, high rate VT, and fibrillation rate zones)and various other characteristics (e.g., sudden onset, stability,physiologic sensors, and morphology, etc.) in order to determine thetype of remedial therapy that is needed (e.g., bradycardia pacing,antitachycardia pacing, cardioversion shocks or defibrillation shocks).

Cardiac signals are also applied to the inputs of an analog-to-digital(ND) data acquisition system 690. The data acquisition system 690 isconfigured to acquire intracardiac electrogram signals, convert the rawanalog data into a digital signal, and store the digital signals forlater processing and/or telemetric transmission to an external device702. The data acquisition system 690 is coupled to the right atrial lead620, the CS lead 624, and the right ventricular lead 630 through theswitch 674 to sample cardiac signals across any pair of desiredelectrodes. The microcontroller 660 is further coupled to a memory 694by a suitable data/address bus 696, wherein the programmable operatingparameters used by the microcontroller 660 are stored and modified, asrequired, in order to customize the operation of pacer/ICD 10 to suitthe needs of a particular patient. Such operating parameters define, forexample, the amplitude or magnitude, pulse duration, electrode polarity,for both pacing pulses and impedance detection pulses as well as pacingrate, sensitivity, arrhythmia detection criteria, and the amplitude,waveshape and vector of each shocking pulse to be delivered to thepatient's heart within each respective tier of therapy. Other pacingparameters include base rate, rest rate and circadian base rate.

Advantageously, the operating parameters of the implantable pacer/ICD 10may be non-invasively programmed into the memory 694 through a telemetrycircuit 700 in telemetric communication with the external device 702,such as a programmer, transtelephonic transceiver or a diagnostic systemanalyzer. The telemetry circuit 700 is activated by the microcontrollerby a control signal 706. The telemetry circuit 700 advantageously allowsintracardiac electrograms and status information relating to theoperation of pacer/ICD 10 (as contained in the microcontroller 660 ormemory 694) to be sent to the external device 702 through an establishedcommunication link 704.

Pacer/ICD 10 further includes an accelerometer or other physiologicsensor 708, sometimes referred to as a “rate-responsive” sensor becauseit can be used to adjust pacing stimulation rate according to theexercise state of the patient. Accordingly, the microcontroller 660 canrespond by adjusting the various pacing parameters (such as rate, AVdelay, VV delay, etc.) at which the atrial and ventricular pulsegenerators, 670 and 672, generate stimulation pulses. However, thephysiological sensor 708 may further be used to detect patient posture,patient activity, blood pressure, and diurnal changes in activity (e.g.,detecting sleep and wake states.) Additionally, as shown, the sensor caninclude 3D accelerometers or acoustic sensors for detecting heart soundsor respiratory sounds as well as changes in posture. While shown asbeing included within pacer/ICD 10, it is to be understood that all orpart of the physiologic sensor 708 may be external to pacer/ICD 10, yetstill be implanted within or carried by the patient. A common type ofphysiological sensor is an activity sensor incorporating anaccelerometer or a piezoelectric crystal, which is mounted within thehousing 640 of pacer/ICD 10. Other types of physiologic sensors are alsoknown, for example, sensors that sense the oxygen content of blood,respiration rate and/or minute ventilation, pH of blood, ventriculargradient, etc.

The pacer/ICD additionally includes a battery 710, which providesoperating power to all of the circuits shown in FIG. 16. The battery 710may vary depending on the capabilities of pacer/ICD 10. If the systemonly provides low voltage therapy, a lithium iodine or lithium copperfluoride cell typically may be utilized. For pacer/ICD 10, which employsshocking therapy, the battery 710 should be capable of operating at lowcurrent drains for long periods, and then be capable of providinghigh-current pulses (for capacitor charging) when the patient requires ashock pulse. The battery 710 should also have a predictable dischargecharacteristic so that elective replacement time can be detected.Accordingly, appropriate batteries are employed.

As further shown in FIG. 16, pacer/ICD 10 is shown as having animpedance measuring circuit 712, which is enabled by the microcontroller660 via a control signal 714. Circuit 712 is used to detect impedancebased either impedance pulses or on the AC currents for the variouspurposes described above. Additional uses for the impedance measuringcircuit include, but are not limited to, lead impedance surveillanceduring the acute and chronic phases for proper lead positioning ordislodgement; detecting operable electrodes and automatically switchingto an operable pair if dislodgement occurs; measuring respiration orminute ventilation; measuring thoracic impedance for determining shockthresholds; detecting when the device has been implanted; measuringrespiration; and detecting the opening of heart valves, etc. Theimpedance measuring circuit 712 is advantageously coupled to the switch774 so that any desired electrode may be used.

In the case where pacer/ICD 10 is intended to operate as an implantablecardioverter/defibrillator (ICD) device, it detects the occurrence of anarrhythmia, and automatically applies an appropriate electrical shocktherapy to the heart aimed at terminating the detected arrhythmia. Tothis end, the microcontroller 660 further controls a shocking circuit716 by way of a control signal 718. The shocking circuit 716 generatesshocking pulses of low (up to 0.5 joules), moderate (0.5-10 joules) orhigh energy (11 to 40 joules or more), as controlled by themicrocontroller 660. Such shocking pulses are applied to the heart ofthe patient through at least two shocking electrodes, and as shown inthis embodiment, selected from the left atrial coil electrode 628, theRV coil electrode 636, and/or the SVC coil electrode 638. The housing640 may act as an active electrode in combination with the RV electrode636, or as part of a split electrical vector using the SVC coilelectrode 638 or the left atrial coil electrode 628 (i.e., using the RVelectrode as a common electrode). Cardioversion shocks are generallyconsidered to be of low to moderate energy level (so as to minimize painfelt by the patient), and/or synchronized with an R-wave and/orpertaining to the treatment of tachycardia. Defibrillation shocks aregenerally of moderate to high energy level (i.e., corresponding tothresholds in the range of 7-40 joules or more), deliveredasynchronously (since R-waves may be too disorganized), and pertainingexclusively to the treatment of fibrillation. Accordingly, themicrocontroller 660 is capable of controlling the synchronous orasynchronous delivery of the shocking pulses.

An internal warning device 699 may be provided for generatingperceptible warning signals to the patient via vibration, voltage orother methods.

Insofar as the acute phase processing techniques described above, themicrocontroller includes an end of acute interval detection unit 701operative to detect the end of the acute phase based, for example, onimpedance stability or based on a programmed durations (such asforty-five days or sixty days.) The microcontroller also includes acardiac decompensation detection system 703 operative to detectingcardiac decompensation events such as, HF, PE and CHF using theabove-described techniques. In this example, system 703 includes anon-impedance-based HF/PE detector 705 operative to detect HF or PE orthe like using non-impedance-based parameters, such as HRV, ventricularER, etc. Detector 705 is provided especially for use during thepost-implant acute phase, though it can operate during the chronic phaseas well. System 703 includes an impedance-based HF/PE detector 707operative to detect HF or PE or the like using impedance-basedparameters (such as CI and PE impedances), once at least one pair ofelectrodes have been properly encapsulated by mature tissues.

Additionally, the microcontroller includes a component encapsulationmaturation assessment system 709 operative to assess the degree ofmaturity of encapsulation of the components of the device, such ascardiac pacing/sensing electrodes using the techniques described above.A maturation-based controller 711 is operative to control various devicefunctions based on the degree of maturation, such as to activate theimpedance-based chronic interval HF/PE detector or to assess theprogression of HF based on changes in the characteristic impedanceresponse (amplitude and phase) of the tissue to bipolar AC impedance, asdiscussed above. Additionally, the microcontroller includes atherapy/CRT/warning/diagnostics controller 713 for controlling thedelivery of therapy including CRT, the generation of warning signals andthe recordation of diagnostics.

Depending upon the implementation, the various components of themicrocontroller may be implemented as separate software modules or themodules may be combined to permit a single module to perform multiplefunctions. In addition, although shown as being components of themicrocontroller, some or all of these components may be implementedseparately from the microcontroller, using application specificintegrated circuits (ASICs) or the like.

As noted, at least some of the techniques described herein can beperformed by (or under the control of) an external device. For the sakeof completeness, an exemplary device programmer will now be described,which includes components for controlling at least some of the functionsand steps already described.

Exemplary Device Programmer

FIG. 17 illustrates pertinent components of an external programmer 702for use in programming the pacer/ICD of FIG. 16 and for performing theabove-described optimization techniques. For the sake of completeness,other device programming functions are also described herein. Generally,the programmer permits a physician or other user to program theoperation of the implanted device and to retrieve and displayinformation received from the implanted device such as IEGM data anddevice diagnostic data. Additionally, the external programmer can beoptionally equipped to receive and display electrocardiogram (EKG) datafrom separate external EKG leads that may be attached to the patient.Depending upon the specific programming of the external programmer,programmer 702 may also be capable of processing and analyzing datareceived from the implanted device and from the EKG leads to, forexample, render preliminary diagnosis as to medical conditions of thepatient or to the operations of the implanted device.

Now, considering the components of programmer 702, operations of theprogrammer are controlled by a CPU 802, which may be a generallyprogrammable microprocessor or microcontroller or may be a dedicatedprocessing device such as an application specific integrated circuit(ASIC) or the like. Software instructions to be performed by the CPU areaccessed via an internal bus 804 from a read only memory (ROM) 806 andrandom access memory 830. Additional software may be accessed from ahard drive 808, floppy drive 810, and CD ROM drive 812, or othersuitable permanent mass storage device. Depending upon the specificimplementation, a basic input output system (BIOS) is retrieved from theROM by CPU at power up. Based upon instructions provided in the BIOS,the CPU “boots up” the overall system in accordance withwell-established computer processing techniques.

Once operating, the CPU displays a menu of programming options to theuser via an LCD display 814 or other suitable computer display device.To this end, the CPU may, for example, display a menu of specificprogrammable parameters of the implanted device to be programmed or maydisplay a menu of types of diagnostic data to be retrieved anddisplayed. In response thereto, the physician enters various commandsvia either a touch screen 816 overlaid on the LCD display or through astandard keyboard 818 supplemented by additional custom keys 820, suchas an emergency VVI (EVVI) key. The EVVI key sets the implanted deviceto a safe VVI mode with high pacing outputs. This ensures lifesustaining pacing operation in nearly all situations but by no means isit desirable to leave the implantable device in the EVVI mode at alltimes.

Once all pacing leads are mounted and the pacing device is implanted,the various parameters are programmed. Typically, the physicianinitially controls the programmer 702 to retrieve data stored within anyimplanted devices and to also retrieve EKG data from EKG leads, if any,coupled to the patient. To this end, CPU 802 transmits appropriatesignals to a telemetry subsystem 822, which provides components fordirectly interfacing with the implanted devices, and the EKG leads.Telemetry subsystem 822 includes its own separate CPU 824 forcoordinating the operations of the telemetry subsystem. Main CPU 802 ofprogrammer communicates with telemetry subsystem CPU 824 via internalbus 804. Telemetry subsystem additionally includes a telemetry circuit826 connected to telemetry wand 828, which, in turn, receives andtransmits signals electromagnetically from a telemetry unit of theimplanted device. The telemetry wand is placed over the chest of thepatient near the implanted device to permit reliable transmission ofdata between the telemetry wand and the implanted device. Herein, thetelemetry subsystem is shown as also including an EKG circuit 834 forreceiving surface EKG signals from a surface EKG system 832. In otherimplementations, the EKG circuit is not regarded as a portion of thetelemetry subsystem but is regarded as a separate component.

Typically, at the beginning of the programming session, the externalprogramming device controls the implanted devices via appropriatesignals generated by the telemetry wand to output all previouslyrecorded patient and device diagnostic information. Patient diagnosticinformation includes, for example, recorded IEGM data and statisticalpatient data such as the percentage of paced versus sensed heartbeats.Device diagnostic data includes, for example, information representativeof the operation of the implanted device such as lead impedances,battery voltages, battery recommended replacement time (RRT) informationand the like. Data retrieved from the pacer/ICD also includes the datastored within the recalibration database of the pacer/ICD (assuming thepacer/ICD is equipped to store that data.) Data retrieved from theimplanted devices is stored by external programmer 702 either within arandom access memory (RAM) 830, hard drive 808 or within a floppydiskette placed within floppy drive 810. Additionally, or in thealternative, data may be permanently or semi-permanently stored within acompact disk (CD) or other digital media disk, if the overall system isconfigured with a drive for recording data onto digital media disks,such as a write once read many (WORM) drive.

Once all patient and device diagnostic data previously stored within theimplanted devices is transferred to programmer 702, the implanteddevices may be further controlled to transmit additional data in realtime as it is detected by the implanted devices, such as additional IEGMdata, lead impedance data, and the like. Additionally, or in thealternative, telemetry subsystem 822 receives EKG signals from EKG leads832 via an EKG processing circuit 834. As with data retrieved from theimplanted device itself, signals received from the EKG leads are storedwithin one or more of the storage devices of the external programmer.Typically, EKG leads output analog electrical signals representative ofthe EKG. Accordingly, EKG circuit 834 includes analog to digitalconversion circuitry for converting the signals to digital dataappropriate for further processing within the programmer. Depending uponthe implementation, the EKG circuit may be configured to convert theanalog signals into event record data for ease of processing along withthe event record data retrieved from the implanted device. Typically,signals received from the EKG leads are received and processed in realtime.

Thus, the programmer receives data both from the implanted devices andfrom optional external EKG leads. Data retrieved from the implanteddevices includes parameters representative of the current programmingstate of the implanted devices. Under the control of the physician, theexternal programmer displays the current programmable parameters andpermits the physician to reprogram the parameters. To this end, thephysician enters appropriate commands via any of the aforementionedinput devices and, under control of CPU 802, the programming commandsare converted to specific programmable parameters for transmission tothe implanted devices via telemetry wand 828 to thereby reprogram theimplanted devices. Prior to reprogramming specific parameters, thephysician may control the external programmer to display any or all ofthe data retrieved from the implanted devices or from the EKG leads,including displays of EKGs, IEGMs, and statistical patient information.Any or all of the information displayed by programmer may also beprinted using a printer 836.

Additionally, CPU 802 also preferably includes a cardiac decompensationdetection system 850 operative to detect HF, PE, CHF or other cardiacdecompensation events based on data signals sent from the implanteddevice. The detection system includes a non-impedance-based HF/PEdetector operative to detect HF/PE or the like based on non-impedancesignals such as HRV, ventricular ER, etc., as discussed above. Thedetection system includes an impedance-based HF/PE detector operative todetect HF/PE or the like based on impedance signals, as also discussedabove. A component maturation assessment system 856 is operative toassess the maturity of encapsulation of device components, also asdescribed above. Control parameters may then be transmitted to thepacer/ICD to program the device to perform deliver therapy to addressany decompensation events that have been detected.

Programmer/monitor 702 also includes an Internet connection unit 838such as a modem to permit direct transmission of data to otherprogrammers via the public switched telephone network (PSTN) or otherinterconnection line, such as a T1 line or fiber optic cable, orwireless telecommunication system. Depending upon the implementation,the modem may be connected directly to internal bus 804 may be connectedto the internal bus via either a parallel port 840 or a serial port 842.Other peripheral devices may be connected to the external programmer viaparallel port 840 or a serial port 842 as well. Although one of each isshown, a plurality of input output (IO) ports might be provided. Aspeaker 844 is included for providing audible tones to the user, such asa warning beep in the event improper input is provided by the physician.Telemetry subsystem 822 additionally includes an analog output circuit845 for controlling the transmission of analog output signals, such asIEGM signals output to an EKG machine or chart recorder.

With the programmer configured as shown, a physician or other useroperating the external programmer is capable of retrieving, processingand displaying a wide range of information received from the implanteddevices and to reprogram the implanted device if needed. Thedescriptions provided herein with respect to FIG. 17 are intended merelyto provide an overview of the operation of programmer and are notintended to describe in detail every feature of the hardware andsoftware of the programmer and is not intended to provide an exhaustivelist of the functions performed by the programmer. Depending upon theimplementation, the various components of the main CPU may beimplemented as separate software modules or the modules may be combinedto permit a single module to perform multiple functions. In addition,although shown as being components of the CPU, some or all of thesecomponents may be implemented separately from the microcontroller, usingASICs or the like.

In general, while the invention has been described with reference toparticular embodiments, modifications can be made thereto withoutdeparting from the spirit and scope of the invention. Note also that theterm “including” as used herein is intended to be inclusive, i.e.“including but not limited to.”

1. A method for use with an implantable medical device for implantwithin a patient, the method comprising: detecting impedance-basedparameters following device implant; assessing a degree of maturation ofencapsulation of components of the implanted device using theimpedance-based parameters; and determining whether the degree ofmaturation has reached an acceptable level and, if so, controlling atleast one impedance-based device function in response thereto.
 2. Themethod of claim 1 wherein controlling at least one device functionincludes: activating an impedance-based detection system to detect apossible cardiac decompensation event within the patient.
 3. The methodof claim 2 wherein the cardiac decompensation event includes one or moreof heart failure (HF), congestive heart failure (CHF) and cardiogenicpulmonary edema (PE).
 4. The method of claim 1 wherein the deviceincludes at least one pair of electrodes implanted within patienttissues and wherein assessing the degree of maturation of encapsulationis performed to assess the degree of maturation of encapsulation of theelectrodes of the pair.
 5. The method of claim 4 wherein assessing thedegree of maturation of encapsulation of the electrodes includes:determining an impedance response for the electrodes as a function offrequency; and determining the degree of maturation of tissuesencapsulating the electrodes based on the impedance frequency response.6. The method of claim 5 wherein determining the impedance frequencyresponse includes determining one or more of impedance magnitude as afunction of frequency and impedance phase as a function of frequency. 7.The method of claim 5 wherein determining the degree of maturation oftissues encapsulating the electrodes includes applying valuesrepresentative of the impedance frequency response to lookup tablesrepresentative of the frequency response in the presence of differenttypes of tissues.
 8. The method of claim 7 wherein the lookup tablesinclude values representative of impedance frequency response in thepresence of one or more of: blood, thrombus, inflammatory tissue,myocardium, fibrosis, and endothelium.
 9. The method of claim 1 whereinthe device includes a plurality of pairs of electrodes implanted withinpatient tissues and wherein assessing the degree of maturation ofencapsulation is performed to identify particular pairs of electrodeswherein maturation has occurred.
 10. The method of claim 1 whereindetecting impedance-based parameters following device implant includesapplying impedance detection pulses to patient tissue between at leastone pair of bipolar electrodes coupled to the device and measuringimpedance parameters in response thereto.
 11. The method of claim 1wherein detecting impedance-based parameters following device implantincludes applying low-level high-frequency alternating current (AC)signals between at least one pair of electrodes coupled to the deviceand measuring impedance signals in response thereto.
 12. The method ofclaim 11 further including characterizing the health of cardiac tissuesbased on the low-level high-frequency AC signals.
 13. The method ofclaim 11 further including tracking progression of heart failure basedon the low-level high-frequency AC signals.
 14. The method of claim 1wherein a housing of the device is equipped with a pair of electrodesand wherein the steps are performed to assess the degree of maturationof encapsulation of the device housing.
 15. The method of claim 1wherein the device is equipped with a physiological sensor adapted toprovide parameters representative of a degree of encapsulation andwherein the steps are performed to assess the degree of maturation ofencapsulation of the device housing based on the physiological sensorparameters.
 16. The method of claim 15 wherein the physiological sensorincludes one or more of an acoustic sensor and a 3D accelerometer andwherein assessing the degree of maturation of encapsulation of thedevice housing based on the physiological sensor parameters is performedbased on a frequency bandwidth of physiological parameters detected bythe sensor.
 17. The method of claim 16 wherein physiological parametersdetected by the sensor include one or more of heart sounds andrespiration sounds and wherein assessing the degree of maturation ofencapsulation of the device housing is performed based on a frequencybandwidth of the sounds detected by the sensor.
 18. A system for usewith an implantable medical device for implant within a patient, thesystem comprising: an impedance detector operative to detectimpedance-based parameters following device implant; and anencapsulation maturation assessment system operative to assess a degreeof maturation of encapsulation of components of the implanted devicebased on the impedance-based parameters.
 19. The system of claim 18further comprising: a maturation-based controller operative to determinewhether the degree of maturation has reached an acceptable level and tocontrol at least one device function in response thereto.
 20. The systemof claim 19 wherein the device function includes detection of a possiblecardiac decompensation event within the patient using an impedance-baseddetection system operative to detect cardiac decompensation eventswithin the patient based on impedance parameters.